Project Summary: The Dana-Farber/Harvard Cancer Center (DF/HCC) is a Harvard-wide, NCI-designated Comprehensive Cancer Center. This training grant is the principal instrument of basic science training at DF/HCC. Our broad goal is to teach young scientists at the predoctoral and postdoctoral levels how to apply emerging technology in genomics and proteomics to fundamental problems in cell division, cell differentiation or cell death ("the three D's" of cancer cell biology) that underlie human neoplastic disease. We propose to appoint 4 predoctoral and 12 postdoctoral scientists per year. Our pre-doctoral trainees will be appointed after their second year of study when they have completed laboratory rotations and chosen one of our mentors as their thesis advisor. We anticipate appointing the strongest postdoctoral trainees. Most of our postdoctoral appointments will be for recent recipients of the Ph.D. or M.D./Ph.D. degrees. Applicants with clinical degrees will also be considered for the program if they have tangible evidence of a commitment to basic cancer research as evidenced by prior research experience. However clinical training is excluded from the program. Laboratory training in cancer research is complemented by a didactic program that prepares our students to exploit a broad range of job opportunities in settings ranging from the small liberal arts college, to academic medical research institutes and the biotechnology industry. Trainee cohesiveness and program identity is addressed on a strategic level with retreats and poster sessions that draw students, postdocs and their mentors from all major components of DF/HCC. On a tactical level, each Department/Division within DF/HCC has journal clubs and seminar programs that provide a sense of local community. Relevance: A distinguishing feature of this training Program is that all of the preceptors have ongoing or developing relationships with DF/HCC clinical programs in one or more of the major human cancers. These "nodal points" between clinicians and basic scientists help to initiate and sustain a cancer focus in our trainees. Many of our prior trainees have already made the transition to scientific independence. Their discovery-oriented basic research has contributed in substantive ways to a new generation of targeted therapies for cancer such as Gleevec, Iressa, Herceptin, and Avastin.